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A role for Bicaudal-D2 in radial cerebellar granule cell migration.

TitleA role for Bicaudal-D2 in radial cerebellar granule cell migration.
Publication TypeJournal Article
Year of Publication2014
AuthorsJaarsma D, van den Berg R, Wulf PS, van Erp S, Keijzer N, Schlager MA, de Graaff E, De Zeeuw CI, R Pasterkamp J, Akhmanova A, Hoogenraad CC
JournalNat Commun
Volume5
Pagination3411
Date Published2014
ISSN2041-1723
KeywordsAnimals, Astrocytes, Blotting, Western, Brain, Cell Movement, Cerebellum, Cerebral Cortex, Humans, Mice, Mice, Inbred C57BL, Mice, Knockout, Mice, Transgenic, Microscopy, Confocal, Microtubule-Associated Proteins, Neuroglia, Neurons, Rats, Time Factors
Abstract

Bicaudal-D (BICD) belongs to an evolutionary conserved family of dynein adaptor proteins. It was first described in Drosophila as an essential factor in fly oogenesis and embryogenesis. Missense mutations in a human BICD homologue, BICD2, have been linked to a dominant mild early onset form of spinal muscular atrophy. Here we further examine the in vivo function of BICD2 in Bicd2 knockout mice. BICD2-deficient mice develop disrupted laminar organization of cerebral cortex and the cerebellum, pointing to impaired radial neuronal migration. Using astrocyte and granule cell specific inactivation of BICD2, we show that the cerebellar migration defect is entirely dependent upon BICD2 expression in Bergmann glia cells. Proteomics analysis reveals that Bicd2 mutant mice have an altered composition of extracellular matrix proteins produced by glia cells. These findings demonstrate an essential non-cell-autonomous role of BICD2 in neuronal cell migration, which might be connected to cargo trafficking pathways in glia cells.

DOI10.1038/ncomms4411
Alternate JournalNat Commun
PubMed ID24614806
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